Lyme disease (LD) and human granulocytic anaplasmosis (HGA), are significant public health threats. LD is caused by Borreliella burgdorferi, B. garinii, B. bavariensis, and B. afzelii and HGA by Anaplasma phagocytophilum (Ap). The CDC estimates there are ~330,000 clinician diagnosed LD cases per year in the US with high numbers in Europe and Canada. Since HGA was designated as a reportable disease in 2009, case numbers have steadily increased. In 2017, 4,151 cases of HGA were reported in the US (a number considered to be a significant underestimate). Current preventive strategies for tick-borne diseases are inadequate and ineffective. With the expansion of the endemic regions for LD and HGA, better recognition of their true incidence, the severity of these diseases, and the potential complications associated with co-infection, a vaccine that protects against multiple tick borne pathogens is needed. In this study we will develop chimeric, linear epitope-based vaccine antigens (chimeritope) for LD and HGA. Proof of principle for chimeritope vaccines has been demonstrated by the successful development of a highly efficacious canine LD vaccine. The basic strategy that was applied in developing the canine vaccine will be employed to construct a human vaccine for both LD and HGA. The chimeric vaccinogens will consist of defined linear epitopes of the OspA, B and C proteins of the LD spirochetes and defined domains of Ap proteins OmpA, Asp14, and AipA. The polyvalent nature of the constructs will provide protection against diverse strains of the LD spirochetes and the causative agent of HGA. The resulting vaccine will offer a new preventive strategy for these significant public health threats. The proposed work is timely, highly significant and addresses an NIH priority area. This study will have broad overall impact as the knowledge gained can be applied in the design of other epitope based multi-valent, multi-disease vaccines.